1. Field of the Invention
The present invention relates to a substitution fluid preparation, and more particularly to a substitution fluid composition which is applied as an energy source, for the suppression of increased protein catabolism in the living body and also for improvement of metabolic acidosis to traumatized patients or severely burned patients in the acute phase, post-operative patients, patients in hepatic insufficiency, patients unable to take foods orally, patients in the state of metabolic (except diabetes-induced) acidosis, all of whom have a common symptom of impaired carbohydrate metabolism.
2. Description of the Prior Art
3-hydroxybutyric acid as the principal ingredient of the substitution fluid composition of the present invention was first found in the urine of some diabetic patients in the form of (R)-3-hydroxybutyric acid and was then deemed to be a useless metabolite occurring in the living body under morbid conditions. Also, as fat-derived energy substrate the object of concern were long-chain fatty acids and the physiological significance of this substance had been rather neglected for a long time. Recently, however, the true physiological significance of this substance has come to be realized as a complementary substrate as substitute of glucose and also as a retainer of caloric homeostasis in the living body.
As to the significance of this substance as energy substrate, it is already known that it is a fat-derived energy substrate, that it is hydrophilic and has an extremely good migration-to-tissues behavior and that it has been used in preference to long-chain fatty acids or glucose in vitro experiments involving tissues of various kinds [(1) Forsey R. G. P., Reid. K. Brosnan J. T. Can. J., "Physiological Pharmacology," 65, 401-406, 1987; (2) Robinson A. M., Wiliamson D. H., "Physiological Reviews," 60 (1), 143-187, 1980], and judging from all these, it can be safely said that this substance is an excellent energy substrate.
When the supply of glucose is unavailable in the living body, it is already known that this substance provides a useful energy substrate, and there are also reports that (RS)-3-sodium hydroxybutyrate administered intravenously to patients under a "very-low-energy diets" therapy proved to be effective in suppressing protein catabolism [(1) Rawan G. L. S., Semple S. L. G., "Lancet," 1, 15-17, 1983; (2) Sherwin R. S., Hendler R. G., Felic P., "The Journal of Clinical Investigation," 55, 1382-1390). These are reports of the cases in which this substance was administered to the living body under the forced condition of scarcity of glucose. The present inventors, however, made rather extensive studies of traumatized patients or severely burned patients in the acute phase, post-operative patients with strong indications of surgical aggression, patients in hepatic insufficiency, patients unable to take foods orally, patients in the state of metabolic (except diabetes-induced) acidosis et al. and found and confirmed that many of such patients were falling into the state of abnormality of metabolism with regard to glucose, amino acid et cetera, this resulting in insufficient utilization of intravenously-administered nutrients such as sugar, amino acids and fat, and they were forced to use energy produced inside through decomposition of protein in their bodies and also that the levels in blood of alanine and glutamine resulting from decomposition of protein were increasing and due to the simultaneous loss of nitrogen, the cumulative nitrogen equilibrium in blood was markedly biased toward the minus side. Patients under such conditions are very likely to have their cells' immune function lowered and suffer from complication by serious infection diseases.